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PHILADELPHIA — TUESDAY, May 29, 2012 (MedPage Today) — Bone is more than an inert repository for calcium and in fact may be an endocrine organ, a researcher suggested here at the American Association of Clinical Endocrinologists meeting.

Bone may secrete blood-borne proteins that influence the function of other body organ systems at a distance from the bone compartment, according to Clifford Rosen, MD, director of clinical and translational research at Maine Medical Center in Portland.

"We now know there are three bone-specific proteins that are just made in bone," Rosen said. These proteins are:

Fibroblast growth factor 23 (FGF-23), which works to control homeostasis of phosphorus and vitamin D

Sclerostin, which is produced by osteocytes in the bone and shuts down bone formation.

Osteocalcin, which influences blood sugar levels and fat deposition

Amgen and several other companies are testing sclerostin antibodies as a potential remedy for osteoporosis or to help fractures or joint replacements heal faster.

Companies also are working to commercialize osteocalcin for the treatment of diabetes.

"The fact that osteocalcin can help diabetics actually is consistent with the idea that exercise improves insulin sensitivity," Rosen said. "Besides the obvious benefit of exercise to muscle, there may be a skeletal component to it as well," Rosen said. "As we exercise, we remodel our skeleton more frequently; we release osteocalcin from our bone and it has an effect on fat cells."

Rosen's own work has shed light on the dynamic process of bone remodeling.

He and his colleagues have shown that bone loss is increased in cold temperatures, but not because of low vitamin D. In mice experiments, they found that insulin-like growth factor-1 (IGF-1) may be involved.

"Mice exposed to cold temperatures tend to lose bone very quickly. We're trying to understand if that environmental factor is influenced through the brain via sympathetic nervous system impulses, and if so, maybe that is part and parcel of why people in northern latitudes have a higher rate of bone osteoporosis," Rosen explained.

Cold temperatures also stimulate brown adipose tissue, or brown fat, which burns energy. But why does that lead to negative bone changes?

The problem occurs when the body does not have enough brown fat, such as in the obese or the elderly. The body will compensate by trying to make brown fat in other sites. It does this by increasing sympathetic impulses, which has a negative effect on bone.

"We initially reported that brown fat has a positive effect on bone," Rosen said. "But that is when the body has a lot of normal brown fat. When it doesn't have this and the body has to compensate, that is actually detrimental."

Studies have also demonstrated that proteins produced by bone cells modulate testosterone release from the testes, suggesting a possible role in reproductive biology.

Rosen said that there's still some skepticism in the medical field about bone being an organ like the heart or kidney. His future research involves investigating the relationship between stem cells and bone cells.

He has already shown that a connection exists in a preclinical experiment. Two groups of mice were fed the same amount of food and water for 12 weeks. One group of mice, however were on a vibrating table, which simulated a kind of low-impact exercise.

The hypothesis was that through the low-impact exercise the stem cells would become bone rather than fat. In fact, they found that the vibrating mice had fewer fat cells and more bone density.

Regarding low-impact exercise for people, Mayo Clinic researchers showed that a raised desk outfitted with a treadmill that allowed people to walk less than 1 mph while they worked burned an extra 100 calories per hour, which could translate into losing nearly 60 lbs a year.

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